1. Field of the Invention
The present invention relates to synthetic pulmonary surfactants for the treatment or prophylaxis of respiratory distress syndrome (RDS) in premature infants and other respiratory disorders. In particular, present the invention relates to a reconstituted surfactant comprising a combination of particular analogues of the native surfactant protein SP-C with analogues of the native surfactant protein SP-B and a phospholipid mixture.
2. Discussion of the Background
The human lung is composed of a large number of small air sacs, called alveoli, in which gases are exchanged between the blood and the air spaces of the lungs. In healthy individuals, this exchange is mediated by the presence of a protein-containing surfactant complex that prevents the lungs from collapsing at the end of expiration.
Lung surfactant complex is composed primarily of lipid and contains minor amounts of various proteins. An absence of adequate levels of this complex results in malfunction of the lung. This syndrome is called Respiratory Distress Syndrome (RDS) and it commonly affects preterm infants.
Said syndrome is effectively treated with modified natural surfactant preparations extracted from animal lungs. Commercially available modified surfactant preparations are, for example, poractant alfa (Curosurf™), derived from porcine lung, calfactant (Infasurf™), extracted form calf lung lavage, and beractant (Survanta™), a chemically modified natural bovine lung extract.
The main constituents of these surfactant preparations are phospholipids, such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), (PG), and surfactant hydrophobic proteins B and C(SP-B and SP-C).
Due to the drawbacks of the surfactant preparations from animal tissues, such as the complication of the production and sterilization processes and possible induction of immune reactions, synthetic surfactants seeking to mime the composition of the modified natural surfactants have been developed. However, according to the available literature, none of the synthetic surfactants developed so far has shown the same efficacy as that of the surfactants extracted from animals.
A possible explanation is that the available reconstituted surfactants developed so far do not reproduce the complete proteinaceous profile of the modified natural surfactants as the former comprise only one proteinaceous (peptide) component.
For these reasons, reconstituted surfactants comprising both analogues of the native surfactant proteins SP-B and SP-C have been proposed in the art, for instance in WO 2008/044109, WO 2008/011559, and WO 2010/139442, all of which are incorporated herein by reference in their entireties.
In WO 2004/105726, which is incorporated herein by reference in its entirety, the use of lipid mixture comprising polyunsaturated phospholipids with the aim of reducing the viscosity of synthetic surfactants has been disclosed.
In spite of that, there is still skepticism regarding the possibility that reconstituted surfactants could achieve the same efficacy in terms of lung compliance of that of the surfactants extracted from animals, in particular in terms of lung gas volumes and grade of alveolar patency at the end of expiration.
So it would be highly advantageous to provide reconstituted surfactants comprising phospholipid mixtures capable of improving the properties in terms of lung compliance.
Thus, there remains a need for reconstituted surfactants with improved properties.